A Wnt signaling pathway is conserved regardless of the difference in the species of organisms, and is known as an important pathway involved in the development, differentiation and maintenance of living organisms. In recent years, however, it is reported that the constitutive activation of the pathway is involved in the development of malignant transformation of fibrosis and cancer. It is known that, particularly in colorectal cancer, melanoma, endometrial cancer, liver cancer and prostate cancer, the Wnt signaling pathway can be activated constitutively by the suppressible mutation of adenomatous polyposis coli (APC) or activating mutation of β-catenin or the like. It is also known that, in pancreatic cancer, hematological cancer, liver cancer and the like, the Wnt signaling pathway can be activated after the treatment with a known anti-tumor agent.
In Non Patent Literatures 1 and 2, it is described that an excellent anti-tumor activity can be achieved by inhibiting the Wnt signaling pathway. In Non Patent Literatures 12, 13 and 14, it is described that an excellent effect on fibrosis can be achieved by inhibiting the Wnt signaling pathway. Thus, the Wnt signaling pathway has attracted attention as a novel target for the treatment of tumors or the treatment of fibrosis.
In Non Patent Literatures 3, 4, 5, 6, 7, 8, 9, 10 and 11, compounds or antibodies capable of inhibiting the Wnt signaling pathways are disclosed, and it is reported that the compounds or the antibodies can act on Tankyrase, Traf2- and Nck-interacting kinase (TNIK), Porcupine, Frizzled Receptor and the like.
Furthermore, compounds each having an octahydro-1H-pyrazino[2,1-c][1,2,4]triazine backbone are known as modulator of the Wnt signaling pathway, and the relationship between the compounds and diseases such as cancer and fibrosis is pointed out (Patent Literatures 1 to 3).